An engineered recombinase
could enable nontoxic, site-specific delivery of therapeutic genes to the
human genome. Recombinases containing zinc finger, DNA-binding domains form
heterodimers capable of site-specific gene delivery but also form homodimers
that can modify off-target genes. In a human cell line, a recombinase containing
an engineered variant of the zinc finger domain exhibited over 500-fold less
homodimerization than a recombinase containing the unmodified domain. In the
cell line, the engineered recombinase was used to deliver human factor
IX or a-galactosidase A into the
genome with no signs of off-target delivery. Future studies could include
developing viral vectors for cell- or tissue-targeted in vivo delivery
of the engineered recombinase.

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